The final goal of this investigation is to achieve a complete understanding of the relationship between the hormonal regulation of renal metabolism and renal function. A number of hormones, including epinephrine and parathyroid hormone, participate in the control of gluconeogenesis and transport in kidney, and one of our long-range goals is to understand the mechanisms by which these hormones elicit specific metabolic and transport effects in this tissue. The particular objective of the present phase of our program is to examine the role of enzyme interactions in the control of gluconeogenesis and transport processes will be integrated with the activation of intracellular multienzyme systems which utilize or produce the transported metabolites. These metabolic and transport processes may be integrated through the action of 3',5'-cyclic AMP and protein kinases acting at the level of the plasma membrane and in the cytosol. The exact mechanisms by which hormones regulate gluconeogenesis and transport in kidney are not yet well understood, however control of the rate and direction of carbohydrate metabolism is thought to occur at specific rate-limiting steps. The phosphorylation and dephosphorylation of specific enzymes acting at these rate-limiting steps by cyclic AMP-dependent protein kinases and phosphoprotein phosphatases may play a critical role in the regulation and coordination of these cellular processes. In our previous studies we isolated and characterized a number of enzymes involved in glycolysis and gluconegenesis in kidney. Cyclic AMP-dependent protein kinase and phosphoprotein phosphatase were also isolated in homogeneous form from swine kidney extracts. Several of these purified enzymes, including glucogen synthetase, phosphofructokinase, 1,6-bisphosphatase and pyruvate kinase were phosphorylated by protein kinase and dephosphorylated by phosphoprotein phosphatase.